Indications for Growth Hormones

Indications for Growth Hormone Therapy in Pediatrics

• Recombinant human growth hormone (rhGH) therapy has been available by prescription since the 1980s and has revolutionized the management of pediatric growth disorders.
• The biological actions of growth hormone are mediated largely through the synthesis of insulin-like growth factor 1 (IGF-1) in the liver and locally at the epiphyseal growth plates, which stimulates chondrocyte proliferation and bone elongation.
• The United States Food and Drug Administration (FDA) has approved eight specific pediatric indications for rhGH treatment to promote linear growth.

FDA-Approved Indications

• Growth Hormone Deficiency (GHD): Approved in 1985, rhGH is the standard treatment for children with isolated GHD or multiple pituitary hormone deficiencies (MPHD) to prevent severe short stature and metabolic complications.
• Turner Syndrome: Approved in 1996, GH therapy improves adult height potential in girls with Turner syndrome, addressing the nearly universal feature of short stature in this population.
• Chronic Renal Insufficiency: Approved in 1993, rhGH is indicated for children with chronic kidney disease who experience growth failure before renal transplantation.
• Prader-Willi Syndrome (PWS): Approved in 2000, GH treatment is used in PWS not only to increase height velocity but also to decrease fat mass and improve lean muscle mass.
• Small for Gestational Age (SGA): Approved in 2001, rhGH is indicated for infants born SGA who fail to demonstrate spontaneous catch-up growth by 2 to 3 years of age.
• Idiopathic Short Stature (ISS): Approved in 2003, this indication is for children with a height below -2.25 standard deviations (the 1.2 percentile) whose growth velocity is unlikely to allow attainment of a normal adult height, provided no other underlying pathology is identified.
• SHOX Gene Mutations: Approved in 2007, therapy is indicated for short stature associated with SHOX gene haploinsufficiency, including Leri-Weill dyschondrosteosis.
• Noonan Syndrome: Approved in 2008, rhGH is utilized to treat the severe linear growth failure commonly associated with this genetic condition.

Pathophysiological and Clinical Management Considerations

• Growth Hormone Deficiency: The recommended initial dose of rhGH for GHD is 0.16 to 0.24 mg/kg/week (22 to 35 µg/kg/day), given as a once-daily subcutaneous injection. The maximal growth response occurs during the first year of therapy, with height velocities often exceeding the 95th percentile for age. In neonates with MPHD, prompt initiation of rhGH is critical to reduce the frequency and severity of severe hypoglycemic episodes.
• Turner Syndrome: GH is often initiated early (between 4 to 6 years of age) at doses around 50 µg/kg/day and can yield an adult height gain of 12 to 17 cm above untreated expectations. In patients with severely compromised height potential, GH may be combined with oxandrolone, a weak nonaromatizable androgen, to add further height gains without inappropriately advancing bone age.
• Chronic Renal Insufficiency: Growth failure in chronic kidney disease is multifactorial, involving decreased IGF bioavailability due to elevated IGF-binding proteins, impaired nutrition, glucocorticoid use, and partial GH insensitivity at the growth plate. Recombinant GH effectively overrides this resistance to increase linear growth rates.
• Prader-Willi Syndrome: Because children with PWS have an increased baseline risk of severe obstructive sleep apnea (OSA) and sudden death, a thorough clinical and polysomnographic evaluation is mandatory before and during rhGH therapy, as GH can stimulate adenotonsillar hypertrophy.
• Small for Gestational Age: While approximately 90% of term SGA infants catch up in growth naturally by 2 years of age, the remainder face compromised adult height. GH therapy accelerates linear growth, though these children require close monitoring due to an inherently increased baseline risk for insulin resistance and adiposity.
• Idiopathic Short Stature: The decision to treat ISS with GH involves a shared decision-making approach, carefully evaluating the physical and psychological burdens of short stature against the variable individual growth responses and the burden of daily injections.
• Monitoring and Adverse Effects: Patients on rhGH require assessments every six months for auxological progression, pubertal staging, and serum IGF-1 levels to optimize dosing and adherence. Potential complications include benign intracranial hypertension, slipped capital femoral epiphysis (SCFE), altered glucose homeostasis, and the unmasking of central hypothyroidism or adrenal insufficiency. Treatment is generally discontinued when the growth velocity drops below 2 to 2.5 cm/year and epiphyseal fusion is confirmed via bone age radiographs.